Di-(2-ethylhcxyl) phthalate reduces progesterone levels and induces apoptosis of ovarian granulosa cell in adult female ICR mice

Di-(2-ethylhexyl) phthalate (DEHP) as an environmental endocrine disruptor is a known reproductive toxicant and carcinogen. The purpose of this study was to evaluate the female reproductive toxicity of DEHP. Sixty ICR female mice were randomized into four groups dosed with 0, 125, 500, or 2 000 mg/kg DEHP by gavage for 16 weeks, 6 days/week. DEHP treatment prolonged duration of the estrous cycle in mice at 500 and 2000 mg/kg DEHP, but no significant effects on estrus phase of the cycle in each group were detected. Exposure to DEHP inhibited secretion of serum progesterone. DEHP arrested granulosa cells at G0/G1 phases and increased proportion of apoptosis cells at 500 and 2000 mg/kg DEHP. There was no significant difference in P450arom mRNA expression among groups. Results demonstrate that DEHP can produce toxicity in female reproductive system.

► The purpose of this study was to evaluate the female reproductive toxicity of DEHP. ► Estrous cycle, serum sex hormone levels, cell cycle, apoptosis, and P450arom mRNA expression of ovarian granulosa cell were determined. ► DEHP treatment prolonged estrous cycle, reduced progesterone levels, arrested cell cycle and increased apoptosis of ovarian granulosa cells. ► Results demonstrate that DEHP can produce toxicity in female reproductive system. ► Studies are useful for assessing the risk from oral exposure and understanding how DEHP affects reproductive function in women.